Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5945_Библиотеки_им_академика_М_И_Перельмана

Carbohydrates, the most abundant organic compounds in nature, play unique roles in health and disease. The complex glycans displayed on the cell surface facing the extracellular space are the key molecules for cell recognition and adhesion in signal­ing pathways and in cell–pathogen interactions[1, 2]. Carbohydrates also trigger immune responses[3–5], and modulate key biological processes in neurodegenera­tion, namely those related to the O-GlcNAc modification (also known as O-GlcNAcylation) of serine (Ser) and threonine (Thr) protein residues in the brain, the dysregulation of which is associated with neurodegenerative diseases [6, 7]. Alzheimer’s disease (AD) is the most common one, affecting 60% of the over 50 mil­lion people with dementia in 2020, a number expected to double every two years, reaching 82 million in 2030 and 152 million in 2050[8]. AD is a chronic and progres­sive disease, resulting from an irreversible degeneration of the brain that causes cognitive impairment, dementia, and ultimately results in death, as no efficient therapeutics are known to control the progression of this pathology. This protein misfolding disease is associated with the formation of soluble Aβ1–42 toxic small oligomers, derived from abnormal cleavage of β-amyloid precursor protein (APP). Their aggregation leads to the formation of fibrils, which give rise to extracellular deposits, the senile plaques[9]. Another AD neuropathological hallmark consists of intracellular neurofibrillary tangles (NFTs) formation due to altered kinase and phosphatase activities, leading to hyperphosphorylation of the Tau protein. This is followed by the aggregation of hyperphosphorylated Tau into paired helical fila­ments and, finally, into NFTs. The aggregation events and associated aggregation stress leads to cell apoptosis[9, 10] (Figure10.1).